scholarly journals Pulmonary exacerbation due to colistin-resistant Stenotrophomonas maltophilia in a Bulgarian cystic fibrosis patient

Folia Medica ◽  
2016 ◽  
Vol 58 (2) ◽  
pp. 136-140 ◽  
Author(s):  
Gergana P. Stoyanova ◽  
Tanya V. Strateva ◽  
Svetlana T. Atanasova ◽  
Dimitrinka S. Miteva ◽  
Vera E. Papochieva ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Stenotrophomonas Maltophilia ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Multidrug Resistant ◽  
Lung Damage ◽  
Pulmonary Exacerbation ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
The Impact

Abstract In patients with cystic fibrosis (CF) lung damage secondary to chronic infection is the main cause of death. Treatment of lung disease to reduce the impact of infection, inflammation and subsequent lung injury is therefore of major importance. As Pseudomonas aeruginosa is the dominant pathogen in CF patients it has been the major target of all treatment strategies, possible antibiotic regimens and recommendations for years. More sophisticated antibiotic therapies introduced over the last decades have helped to improve the prognosis in cystic fibrosis, but then new multidrug-resistant pathogens emerged. We present a case of cystic fibrosis in a 16-year-old boy with pulmonary exacerbation due to colistin-resistant Stenotrophomonas maltophilia. This case raises some interesting questions regarding the antibiotic policy and treatment options in our country for patients with CF and multidrug-resistant strains. Colistin is used at present in Bulgaria as a strategic last option for the CF patients but with the advent of new more drug-resistant strains therapeutic approach should change - for instance, there should be restrictions imposed on the use of levofloxacin and trimethoprim/sulfamethoxazole which are regarded as “cheap and not so potent” antibiotics suitable for any infection and use them only in strict dependence on the respective culture results.

scholarly journals Cystic Fibrosis-AssociatedStenotrophomonas maltophiliaStrain-Specific Adaptations and Responses to pH

2019 ◽  
Vol 201 (7) ◽  
Author(s):  
Tara Gallagher ◽  
Joann Phan ◽  
Andrew Oliver ◽  
Alexander B. Chase ◽  
Whitney E. England ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Stenotrophomonas Maltophilia ◽  
Opportunistic Infections ◽  
Expression Profiles ◽  
Bacterial Colonization ◽  
Low Ph ◽  
Lung Damage ◽  
Ph Gradients ◽  
Content Type ◽  
The Impact

ABSTRACTThe airway fluids of cystic fibrosis (CF) patients contain local pH gradients and are more acidic than those of healthy individuals. pH is a critical factor that is often overlooked in studies seeking to recapitulate the infection microenvironment. We sought to determine the impact of pH on the physiology of a ubiqituous yet understudied microbe,Stenotrophomonas maltophilia. Phylogenomics was first used to reconstruct evolutionary relationships between 74 strains ofS. maltophilia(59 from CF patients). Neither the core genome (2,158 genes) nor the accessory genome (11,978 genes) distinguish the CF and non-CF isolates; however, strains from similar isolation sources grouped into the same subclades. We grew two human and six CFS. maltophiliaisolates from different subclades at a range of pH values and observed impaired growth and altered antibiotic tolerances at pH 5. Transcriptomes revealed increased expression of both antibiotic resistance and DNA repair genes in acidic conditions. Although the gene expression profiles ofS. maltophiliain lab cultures and CF sputum were distinct, we found that the same genes associated with low pH were also expressed during infection, and the higher pH cultures were more similar to sputum metatranscriptomes. Our findings suggest thatS. maltophiliais not well adapted to acidity and may cope with low pH by expressing stress response genes and colonizing less acidic microenvironments. As a whole, our study underlines the impact of microenvironments on bacterial colonization and adaptation in CF infections.IMPORTANCEUnderstanding bacterial responses to physiological conditions is an important priority for combating opportunistic infections. The majority of CF patients succumb to inflammation and necrosis in the airways, arising from chronic infection due to ineffective mucociliary clearance. Steep pH gradients characterize the CF airways but are not often incorporated in standard microbiology culture conditions.Stenotrophomonas maltophiliais a prevalent CF opportunistic pathogen also found in many disparate environments, yet this bacterium’s contribution to CF lung damage and its response to changing environmental factors remain largely understudied. Here, we show that pH impacts the physiology and antibiotic susceptibility ofS. maltophilia, with implications for the development of relevantin vitromodels and assessment of antibiotic sensitivity.

scholarly journals Antimicrobial Susceptibility and Synergy Studies of Stenotrophomonas maltophilia Isolates from Patients with Cystic Fibrosis

2004 ◽  
Vol 48 (1) ◽  
pp. 168-171 ◽  
Author(s):  
Pablo San Gabriel ◽  
Juyan Zhou ◽  
Setareh Tabibi ◽  
Yunhua Chen ◽  
Marco Trauzzi ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Antimicrobial Susceptibility ◽  
Stenotrophomonas Maltophilia ◽  
Antimicrobial Agents ◽  
Active Agent ◽  
The United States ◽  
Multidrug Resistant ◽  
Resistant Organism ◽  
High Concentrations ◽  
The Impact

ABSTRACT Stenotrophomonas maltophilia is a newly emerging pathogen being detected with increasing frequency in patients with cystic fibrosis (CF). The impact of this multidrug-resistant organism on lung function is uncertain. The optimal treatment for S. maltophilia in CF patients is unknown. We studied the in vitro activity of ten antimicrobial agents, and conducted synergy studies by using checkerboard dilutions of eight pairs of antimicrobial agents against strains isolated from 673 CF patients from 1996 to 2001. This represents approximately 7 to 23% of the CF patients in the United States who harbor S. maltophilia annually. Doxycycline was the most active agent and inhibited 80% of 673 initial patient isolates, while trimethoprim-sulfamethoxazole inhibited only 16%. High concentrations of colistin proved more active than high concentrations of tobramycin and gentamicin. Serial isolates (n = 151) from individual patients over time (median, 290 days) showed minimal changes in resistance. Synergistic or additive activity was demonstrated by trimethoprim-sulfamethoxazole paired with ticarcillin-clavulanate (65% of strains), ciprofloxacin paired with ticarcillin-clavulanate (64% of strains), ciprofloxacin paired with piperacillin-tazobactam (59% of strains), trimethoprim-sulfamethoxazole paired with piperacillin-tazobactam (55% of strains), and doxycycline paired with ticarcillin-clavulanate (49% of strains). In all, 522 (78%) isolates were multidrug resistant (i.e., resistant to all agents in two or more antimicrobial classes) but 473 (91%) of these were inhibited by at least one antimicrobial combination (median, four; range, one to eight). To determine appropriate treatment for patients with CF, it is important to monitor the prevalence, antimicrobial susceptibility, and clinical impact of S. maltophilia in this patient population.

scholarly journals In Vitro Activities of β-Lactam–β-Lactamase Inhibitor Antimicrobial Agents against Cystic Fibrosis Respiratory Pathogens

2019 ◽  
Vol 64 (1) ◽  
Author(s):  
Lindsay J. Caverly ◽  
Theodore Spilker ◽  
Linda M. Kalikin ◽  
Terri Stillwell ◽  
Carol Young ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Respiratory Pathogens ◽  
Content Type ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Increased Activity ◽  
Lactamase Inhibitor

ABSTRACT We tested the in vitro activities of ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, piperacillin-tazobactam, and 11 other antimicrobial agents against 420 Burkholderia, Achromobacter, Stenotrophomonas, and Pandoraea strains, 89% of which were cultured from respiratory specimens from persons with cystic fibrosis. Among the β-lactam–β-lactamase inhibitor agents, meropenem-vaborbactam had the greatest activity against Burkholderia and Achromobacter, including multidrug-resistant and extensively-drug-resistant strains. None of the newer β-lactam–β-lactamase combination drugs showed increased activity compared to that of the older agents against Stenotrophomonas maltophilia or Pandoraea spp.

scholarly journals Multidrug-Resistant Gram-Negative Bacilli: A Retrospective Study of Trends in a Tertiary Healthcare Unit

Medicina ◽  
2018 ◽  
Vol 54 (6) ◽  
pp. 92 ◽  
Author(s):  
Delia Muntean ◽  
Florin-George Horhat ◽  
Luminița Bădițoiu ◽  
Victor Dumitrașcu ◽  
Iulia-Cristina Bagiu ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Metabolic Diseases ◽  
Treatment Options ◽  
Acquired Resistance ◽  
Multidrug Resistant ◽  
Trend Test ◽  
Gram Negative ◽  
Increasing Trend ◽  
Tertiary Healthcare ◽  
Resistant Strains

Background and objective: Bacterial multidrug resistance is particularly common in Gram-negative bacilli (GNB), with important clinical consequences regarding their spread and treatment options. The aim of this study was to investigate the trend of multidrug-resistant GNB (MDR-GNB) in high-risk hospital departments, between 2000–2015, in intervals of five years, with the intention of improving antibiotic therapy policies and optimising preventive and control practices. Materials and methods: This is an observational, retrospective study performed in three departments of the most important tertiary healthcare unit in the southwestern part of Romania: the Intensive Care Unit (ICU), the General Surgery Department (GSD), and the Nutrition and Metabolic Diseases Department (NMDD). MDR was defined as acquired resistance to at least one agent in three or more antimicrobial categories. Trends over time were determined by the Cochran–Armitage trend test and linear regression. Results: During the study period, a total of 2531 strains of MDR-GNB were isolated in 1999 patients: 9.20% in 2000, 18.61% in 2005, 37.02% in 2010, and 35.17% in 2015. The most significant increasing trend was recorded in the ICU (gradient = 7.63, R² = 0.842, p < 0.001). The most common MDR-GNB in the ICU was isolated from bronchoalveolar aspiration samples. Concerning the proportion of different species, most of the changes were recorded in the ICU, where a statistically significant increasing trend was observed for Proteus mirabilis (gradient = 2.62, R2 = 0.558, p < 0.001) and Acinetobacter baumannii (gradient = 2.25, R2 = 0.491, p < 0.001). Analysis of the incidence of the main resistance phenotypes proportion identified a statistically significant increase in carbapenem resistance in the ICU (Gradient = 8.27, R² = 0.866, p < 0.001), and an increased proportion of aminoglycoside-resistant strains in all three departments, but more importantly in the ICU and GSD. Conclusion: A statistically significant increasing trend was observed in all three departments; the most significant one was recorded in the ICU, where after 2010, carbapenem-resistant strains were isolated.

scholarly journals The Biology and Role of Interleukin-32 in Tuberculosis

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Wu Li ◽  
Wanyan Deng ◽  
Jianping Xie
Keyword(s):  
Multidrug Resistant ◽  
Drug Resistant ◽  
Host Molecule ◽  
Tuberculosis Control ◽  
Promising Alternative ◽  
Extensively Drug Resistant ◽  
Important Host ◽  
Resistant Strains ◽  
Drug Resistant Strains

Tuberculosis, caused by Mycobacterium tuberculosis, remains a leading cause of morbidity and mortality globally, with nearly 10.4 million new cases of incidence and over 1.7 million deaths annually. Drug-resistant M. tuberculosis strains, especially multidrug-resistant or extensively drug-resistant strains, have further intensified the problem associated with tuberculosis control. Host-directed therapy is a promising alternative for tuberculosis control. IL-32 is increasingly recognized as an important host molecule against tuberculosis. In this review, we highlight the proinflammatory properties of IL-32 and the mode of action of IL-32 in mycobacterial infections to inspire the development of novel immunity-based countermeasures and host-directed therapies against tuberculosis.

Global priority pathogens: virulence, antimicrobial resistance and prospective treatment options

2020 ◽  
Vol 15 (8) ◽  
pp. 649-677 ◽  
Author(s):  
Juliana C de M Campos ◽  
Luis CM Antunes ◽  
Rosana BR Ferreira
Keyword(s):  
Treatment Options ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Salmonella Spp ◽  
Multidrug Resistant Bacteria ◽  
Major Threat ◽  
Global Priority ◽  
Resistant Strains ◽  
Therapeutic Alternatives ◽  
New Strategies

Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Salmonella spp. are part of a group of pathogens that pose a major threat to human health due to the emergence of multidrug-resistant strains. Moreover, these bacteria have several virulence factors that allow them to successfully colonize their hosts, such as toxins and the ability to produce biofilms, resulting in an urgent need to develop new strategies to fight these pathogens. In this review, we compile the most up-to-date information on the epidemiology, virulence and resistance of these clinically important microorganisms. Additionally, we address new therapeutic alternatives, with a focus on molecules with antivirulence activity, which are considered promising to combat multidrug-resistant bacteria.

scholarly journals Synergistic Activity of Colistin-Containing Combinations against Colistin-ResistantEnterobacteriaceae

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Thea Brennan-Krohn ◽  
Alejandro Pironti ◽  
James E. Kirby
Keyword(s):  
Treatment Options ◽  
Multidrug Resistant ◽  
Synergistic Activity ◽  
Gram Negative ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Resistant Strains ◽  
Bacterial Outer Membrane ◽  
Time Kill ◽  
Synergistic Combinations

ABSTRACTResistance to colistin, a polypeptide drug used as an agent of last resort for the treatment of infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria, including carbapenem-resistantEnterobacteriaceae(CRE), severely limits treatment options and may even transform an XDR organism into one that is pan-resistant. We investigated the synergistic activity of colistin in combination with 19 antibiotics against a collection of 20 colistin-resistantEnterobacteriaceaeisolates, 15 of which were also CRE. All combinations were tested against all strains using an inkjet printer-assisted digital dispensing checkerboard array, and the activities of those that demonstrated synergy by this method were evaluated against a single isolate in a time-kill synergy study. Eighteen of 19 combinations demonstrated synergy against two or more isolates, and the 4 most highly synergistic combinations (colistin combined with linezolid, rifampin, azithromycin, and fusidic acid) were synergistic against ≥90% of strains. Sixteen of 18 combinations (88.9%) that were synergistic in the checkerboard array were also synergistic in a time-kill study. Our findings demonstrate that colistin in combination with a range of antibiotics, particularly protein and RNA synthesis inhibitors, exhibits synergy against colistin-resistant strains, suggesting that colistin may exert a subinhibitory permeabilizing effect on the Gram-negative bacterial outer membrane even in isolates that are resistant to it. These findings suggest that colistin combination therapy may have promise as a treatment approach for patients infected with colistin-resistant XDR Gram-negative pathogens.

scholarly journals What does first-line therapy mean for paediatric multiple sclerosis in the current era?

2020 ◽  
pp. 135245852093764
Author(s):  
Yael Hacohen ◽  
Brenda Banwell ◽  
Olga Ciccarelli
Keyword(s):  
Multiple Sclerosis ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Cognitive Outcome ◽  
First Line ◽  
First Line Therapy ◽  
Highly Active ◽  
Paediatric Multiple Sclerosis ◽  
The Impact

Paediatric multiple sclerosis (MS) is associated with higher relapse rate, rapid magnetic resonance imaging lesion accrual early in the disease course and worse cognitive outcome and physical disability in the long term compared to adult-onset disease. Current treatment strategies are largely centre-specific and reliant on adult protocols. The aim of this review is to examine which treatment options should be considered first line for paediatric MS and we attempt to answer the question if injectable first-line disease-modifying therapies (DMTs) are still an optimal option. To answer this question, we review the effects of early onset disease on clinical course and outcomes, with specific considerations on risks and benefits of treatments for paediatric MS. Considering the impact of disease activity on brain atrophy, cognitive impairment and development of secondary progressive MS at a younger age, we would recommend treating paediatric MS as a highly active disease, favouring the early use of highly effective DMTs rather than injectable DMTs.

Antituberculosis activities of clofazimine and its new analogs B4154 and B4157.

1996 ◽  
Vol 40 (3) ◽  
pp. 633-636 ◽  
Author(s):  
V M Reddy ◽  
G Nadadhur ◽  
D Daneluzzi ◽  
J F O'Sullivan ◽  
P R Gangadharam
Keyword(s):  
Multidrug Resistant ◽  
New Drugs ◽  
Drug Resistant ◽  
Antituberculosis Drugs ◽  
Resistant Tuberculosis ◽  
Chemotherapeutic Activity ◽  
Resistant Strains ◽  
Intracellular Activities ◽  
Moderate Resistance ◽  
Drug Resistant Strains

In our efforts to develop new drugs for the treatment of tuberculosis, especially that caused by multidrug-resistant strains, we investigated clofazimine (CFM) and two of its analogs, B4154 and B4157, for their antituberculosis activities. Twenty M. tuberculosis strains were tested, including 16 drug-resistant strains (strains resistant to one or more antituberculosis drugs), for their susceptibilities to these three agents. All of the strains were found to be susceptible to B4154 and B4157, and one strain showed moderate resistance to CFM. The MICs of B4154, B4157, and CFM at which 90% of strains were inhibited were 0.25, 0.12, and < or = 1.0 microgram/ml, respectively. The intracellular activities of CFM and B4157 were superior to that of B4154. The chemotherapeutic activities of the three compounds were evaluated in C57BL/6 mice. At a dose of 20 mg/kg of body weight, the activity of CFM was slightly superior to that of B4157; however, both compounds prevented mortality and caused a significant reduction in the numbers of CFU in the lungs and spleens. The animals treated with B4157 showed less pigmentation than animals treated with CFM. The chemotherapeutic activity of CFM was comparable to those of rifampin and isoniazid. Complete susceptibility of multidrug-resistant strains to CFM and B4157 and the therapeutic efficacies of these compounds against mouse tuberculosis make these drugs attractive agents for the treatment of drug-resistant tuberculosis.

Modern Clinician-initiated Clinical Trials to Determine Optimal Therapy for Multidrug-resistant Gram-negative Infections

2019 ◽  
Vol 71 (2) ◽  
pp. 433-439
Author(s):  
Adam G Stewart ◽  
Patrick N A Harris ◽  
Mark Chatfield ◽  
Scott R Evans ◽  
David van Duin ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Multidrug Resistant ◽  
Small Sample ◽  
Consensus Approach ◽  
Gram Negative ◽  
Therapeutic Trials ◽  
Clinical Trial Designs ◽  
Small Sample Sizes

Abstract Treatment options for multidrug-resistant (MDR) gram-negative infection are growing. However, postregistration, pragmatic, and clinician-led clinical trials in this field are few, recruit small sample sizes, and experience deficiencies in design and operations. MDR gram-negative therapeutic trials are often inefficient, only evaluating a single antibiotic or strategy at a time. Novel clinical trial designs offer potential solutions by attempting to obtain clinically meaningful conclusions at the end or during a trial, for many treatment strategies, simultaneously. An integrated, consensus approach to MDR gram-negative infection trial design is crucial.

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